Method of detecting endotracheal tube misplacement

ABSTRACT

A method of intubating a subject is disclosed. The method comprises inserting an endotracheal tube into the tracheal airway of the subject; inflating a cuff associated with the endotracheal tube within the airway below the vocal cords; measuring a level of at least one measure being indicative of leakage of secretion past the cuff to the lungs; comparing the level of the measure with an optimal level of the measure; and adjusting inflation of the cuff based on the comparison so as to generally minimize leakage of secretion from above the cuff to the lungs, while minimizing pressure associated damages to the airway. The measure(s) can be carbon dioxide concentration, a proxy measure from which such concentration can be inferred, or the level of one or more additives delivered to a subject during intubation.

RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.12/984,673 filed on Jan. 5, 2011, which is a continuation of U.S. patentapplication Ser. No. 11/990,694, filed on Feb. 20, 2008, now U.S. Pat.No. 8,424,529, which is a National Phase of PCT Patent Application No.PCT/IL2006/000974 having International Filing Date of Aug. 21, 2006,which claims the benefit of priority of U.S. Provisional PatentApplication Nos. 60/754,191 filed on Dec. 28, 2005, 60/721,965 filed onSep. 30, 2005, and 60/710,678 filed on Aug. 24, 2005. The contents ofthe above Applications are all incorporated herein by reference.

FIELD AND BACKGROUND OF THE INVENTION

The present invention relates to intubation and, more particularly, to asystem and method for performing endotracheal intubation and adjustingendotracheal tube cuff filling.

In the medical treatment of patients requiring breathing assistance, itis common to insert an endotracheal tube into the trachea of thepatient, by way of the mouth, nose or any other surgically createdopening. One end of the endotracheal tube is connected to a ventilatorwhich periodically forces air into the lungs through the tube. The innerend of the tube is typically provided with an inflatable cuff which isinflated by conventional means subsequently to the insertion of the tubeinto the trachea. The inflated cuff is supposed to provides a sealagainst the interior wall of the trachea.

In such cuffed endotracheal tubes, if the cuff is brought into contactwith the inner wall of the trachea under too high pressure, normal bloodflow in the mucosa is disturbed due to excess pressure for capillaryvessels at the contact portion, resulting in tissue ischemia orinadequate blood flow. Prolonged ischemia can cause varying degrees ofinjury, such as erosion of the mucosa, destruction of the trachealcartilage rings, or segmental tracheomalacia with dilation of thetrachea. Even more dramatic is full thickness erosion which may resultin perforation of the innominate artery anteriorly or perforation of theesophagus posteriorly. Patients requiring long term ventilatory supportoftentimes developed late complications of tracheal stenosis, from mildto incapacitating obstruction.

On the other hand, if the cuff is brought into contact with the innerwall of the trachea under too low a pressure, the artificial respirationcan be inhibited due to a leakage of anesthetic gas, oxygen or air.Furthermore, when the pressure is low, bodily secretions, mucous orother unwanted fluids can pass progressively between the inner surfaceof the trachea and the outer surface of the cuff. These secretions canpass from the trachea and enter the bronchi, potentially to cause lunginfections.

It is therefore necessary to maintain the cuff contact pressure on theinner wall of the trachea at an appropriate level so as to prevent theleakage of air from between the inflated cuff and the tracheal wallduring mechanical ventilation, while at the same time maintaining thenecessary blood flow in the capillaries at the contact portion.

To prevent tissue damage caused by prolonged pressure from the cuff, thephysician periodically deflates and re-inflates the cuff. However, thisprocedure is rarely done frequently enough or for a long enough periodof time to allow adequate reperfusion of the tissue. Therefore, thisprocedure does not dependably prevent tracheal wall ischemia.

A variety of endotracheal tubes have been developed. For example, U.S.Pat. No. 4,159,722 discloses an improved pressure regulator for aninflatable cuff on an endotracheal tube which prevents relatively rapidpressure increases and permits relatively slow pressure increases. Thepressure regulator provides a visual indication of the air pressure inthe cuff.

U.S. Pat. No. 4,305,392 attempts to solve the problem of secretionleakage by suctioning. The endotracheal tube is combined with a suctiondevice in a form of a chamber with suction ports for suctioning outfluids in the trachea above the cuff and for introducing medicinalfluids into the trachea.

U.S. Pat. No. 4,501,273 attempts to solve the problem of leakage bycontrolling the cuff. The pressure within the cuff automaticallyincreases in proportion with the increases in pressure fed to theinterior of the endotracheal tube, thereby preventing breakdown orleakage in the seal between the inflated cuff and the trachea wall.

U.S. Pat. No. 5,765,559 addresses the issue of constant static pressureexerted by the cuff on the tracheal wall which, during prolongedsurgery, may result in tracheal stenosis. The proposed solution includesa cuffed endotracheal tube having a plurality of cuff rings, each beingcapable of inflating and deflating periodically such that when one ormore of the cuff rings deflate the others remains inflated. This reducesdamage to the tracheal wall due to constant pressure on fixed locations.

None of the above and other prior art technologies, however, monitorleakage at the contact area between the cuff and the tracheal innerwall.

A different approach is disclosed in International Patent Application,Publication No. WO 2002/076279 and U.S. Pat. No. 6,843,250 both filed bythe Inventor of the present invention. In this approach, theconcentration of carbon dioxide is monitored in the patient's airwaybetween the cuff and the vocal cords.

Based on the monitoring, the inflation of the cuff is adjusted so as toprevent the leakage of carbon dioxide past the cuff. The inflation ofthe cuff is adjusted to provide a minimum inflation pressure, whichprevents leakage of carbon dioxide past the cuff.

Additional prior arts of relevance include U.S. Pat. Nos. 3,504,676,3,794,036, 4,305,392, 4,770,170, 4,825,862, 5,067,497, 5,579,762,5,582,166, 5,582,167, 5,752,921, 5,819,723, 5,937,861 and 6,062,223.

The present invention provides solutions to the problems associated withprior art endotracheal intubation techniques.

SUMMARY OF THE INVENTION

The background art does not teach the optimization of endotracheal tubecuff filling by measuring a measure indicative of secretion leakage pastthe cuff to the lungs and comparing the indicative measure with anoptimal level of the measure. The background art does not teach theoptimal value of carbon dioxide concentration nor does it teach anymeasure other than carbon dioxide concentration. Furthermore, thebackground art does not teach the use of additives to identify formationof leakage duct near the cuff for the purpose of cuff adjustment.

The present invention provides a method and system which can beefficiently used in intubation procedures in which an endotracheal tubeis introduced into the tracheal airway and a cuff is inflated within theairway below the vocal cords.

In various exemplary embodiments of the invention the method and systemof the present invention perform measurement of one or more measuresbeing indicative of secretion leakage past the cuff, compare themeasure(s) to one or more optimal values of the measure(s) and adjustcuff filling based on the comparison. The measure(s) according topreferred embodiments of the present invention can be carbon dioxideconcentration, a proxy measure from which such concentration can beinferred, or the level of one or more additives delivered to a subjectduring intubation so as to identify formation of leakage duct near thecuff.

When one or more additives are delivered to the subject, they can bedelivered either to the lungs, through the main lumen of theendotracheal tube (e.g., by mixing the breathing gas with the additive),or to a location above the cuff between the internal wall of thesubject's airway and the external wall of the endotracheal tube. Thelevel of the additive is monitored at a monitoring location which isselected according to the delivery technique. For example, when thedelivery is through the main lumen of the endotracheal tube, themonitoring location can be above the cuff between the internal wall ofthe subject's airway and the external wall of the endotracheal tube; andwhen the delivery is to a location above the cuff between the airway andthe endotracheal tube, the monitoring location can be below the cuff orwithin the main lumen of the endotracheal tube.

Thus, according to one aspect of the present invention there is provideda method of intubating a subject having a tracheal airway ending withlungs. The method comprises: inserting an endotracheal tube into theairway; inflating a cuff associated with the endotracheal tube withinthe airway below the vocal cords; measuring a level of at least onemeasure being indicative of leakage of secretion past the cuff to thelungs; comparing the level of the measure(s) with an optimal level ofthe measure(s); and adjusting inflation of the cuff based on thecomparison so as to generally minimize leakage of secretion from abovethe cuff to the lungs, while minimizing pressure associated damages tothe airway.

According to further features in preferred embodiments of the inventiondescribed below, the measure is other than carbon dioxide concentrationbetween the cuff and the vocal cords

According to still further features in the described preferredembodiments the method further comprises performing at least onemeasurement of ambient carbon dioxide partial pressure, and utilizingthe ambient carbon dioxide partial pressure for setting the value of theoptimal level.

According to still further features in the described preferredembodiments the measurement of ambient carbon dioxide partial pressureis performed continuously, so as to provide a series of real-time valuesof the ambient carbon dioxide partial pressure.

According to still further features in the described preferredembodiments the ambient carbon dioxide partial pressure is used as areference partial pressure, whereby the optimal level corresponds to acarbon dioxide partial pressure being larger than the reference partialpressure by about 4 mm Hg.

According to still further features in the described preferredembodiments the optimal level corresponds to a partial carbon dioxidepressure of from about 0.32 mm Hg to about 4 mm Hg.

According to another aspect of the present invention there is provided amethod of intubating a subject having an airway ending with lungs andvocal cords. The method comprises: inserting an endotracheal tube intothe airway; inflating a cuff associated with the endotracheal tubewithin the airway below the vocal cords; delivering a breathing gas andat least one identifiable additive through the endotracheal tube;monitoring a level of the at least one identifiable additive at amonitoring location in the body of the subject; and adjusting inflationof the cuff based on the monitoring so as to generally minimize leakageof secretion from above the cuff to the lungs, while minimizing pressureassociated damages to the airway.

According to further features in preferred embodiments of the inventiondescribed below, the method further comprises signaling when a level ofthe at least one identifiable additive exceeds an optimal level of theat least one identifiable additive.

According to still further features in the described preferredembodiments the monitoring location is at a nostril of the subject,oropharynx, above the cuff between the endotracheal tube and walls ofthe airway and/or below the cuff and adjacent thereto.

According to still further features in the described preferredembodiments the method further comprises suctioning secretions at asuctioning location in the airway above the cuff.

According to still further features in the described preferredembodiments the insertion of the endotracheal tube comprises insertingat least one of a measuring conduit and a suctioning conduit.

According to still further features in the described preferredembodiments adjustment of the cuff inflation is performed manually.

According to still further features in the described preferredembodiments adjustment of the cuff inflation is performed automatically.

According to yet another aspect of the present invention there isprovided a system for intubating a subject having an airway ending withlungs, comprising: an endotracheal tube, adapted to be inserted into theairway and being associated with a cuff capable of being inflated belowthe vocal cords; and a measuring device for measuring at least onemeasure being indicative of leakage of secretion from above the cuff tothe lungs.

According to further features in preferred embodiments of the inventiondescribed below, the measuring device is designed and configured tosignal when a level of the at least one measure exceeds the optimallevel.

According to still further features in the described preferredembodiments the system further comprises the optimal level is apredetermined optimal level.

According to still further features in the described preferredembodiments the measuring device is designed and configured to signalwhen a level of the measure(s) exceeds an optimal level corresponding toa partial carbon dioxide pressure of from about 0.32 mm Hg to about 4 mmHg.

According to still further features in the described preferredembodiments the measuring device is designed an configured to perform atleast one measurement of ambient carbon dioxide partial pressure,whereby the ambient carbon dioxide partial pressure is utilized forsetting the value of the optimal level.

According to an additional aspect of the present invention there isprovided a system for intubating a subject having an airway ending withlungs. The system comprises: an endotracheal tube, adapted to beinserted into the airway and being associated with a cuff capable ofbeing inflated below the vocal cords; an additive delivering unitoperatively associated with the endotracheal tube and configured todeliver at least one identifiable additive through the endotrachealtube; and a measuring device for measuring a level of the at least oneidentifiable additive.

According to further features in preferred embodiments of the inventiondescribed below, the measuring device is designed and configured tosignal when a level of the at least one identifiable additive exceeds anoptimal level of the at least one identifiable additive.

According to still further features in the described preferredembodiments the endotracheal tube comprises an additive delivery conduitconfigured to deliver the at least one identifiable additive.

According to still further features in the described preferredembodiments the additive delivery conduit is disposed within a lumen ofthe endotracheal tube.

According to still further features in the described preferredembodiments the additive delivery conduit is externally coupled to orembedded in a wall of the endotracheal tube.

According to still further features in the described preferredembodiments the system further comprises an inflating device foradjusting inflation of the cuff based on signals received from themeasuring device so as to generally minimize leakage of secretion fromabove the cuff to the lungs, while minimizing pressure associateddamages to the airway.

According to still further features in the described preferredembodiments the measuring device comprises a display device fordisplaying the level of the at least one measure.

According to still further features in the described preferredembodiments the system further comprises an alerting unit being incommunication with the measuring device for producing an alert inresponse to signals received from the measuring device.

According to still further features in the described preferredembodiments the inflating device is in communication with the measuringdevice, thereby forming therewith a closed loop control.

According to still further features in the described preferredembodiments the system further comprises a measuring conduit extendingfrom the measuring device to the airway above the cuff.

According to still further features in the described preferredembodiments the system further comprises a suctioning device operativefor suctioning secretions at a suctioning location in the airway abovethe cuff.

According to still further features in the described preferredembodiments the system further comprises a suctioning conduit extendingfrom the suctioning device to the suctioning location.

According to still further features in the described preferredembodiments the system further comprises a measuring and suctioningconduit, extending to the suctioning location, the a measuring andsuctioning conduit being coupled to the measuring device and thesuctioning device so as to facilitate the measuring and the suctioningat the location.

According to still further features in the described preferredembodiments the measuring and suctioning conduit is disposed internallywithin the endotracheal tube.

According to still further features in the described preferredembodiments the measuring and suctioning conduit is disposed externallyto the endotracheal tube.

According to still further features in the described preferredembodiments the measuring and suctioning conduit is embedded in a wallof the endotracheal tube.

According to still further features in the described preferredembodiments the measurement is performed at a nostril of the subject.

According to still further features in the described preferredembodiments the measurement is performed at the oropharynx of thesubject.

According to still further features in the described preferredembodiments the measurement is performed above the cuff below the vocalcords of the subject.

According to still further features in the described preferredembodiments the measurement is performed below the cuff and adjacentthereto.

According to still further features in the described preferredembodiments the at least one measure comprises carbon dioxideconcentration between the cuff and the vocal cords.

According to still further features in the described preferredembodiments the at least one measure comprises carbon dioxideconcentration above the vocal cords.

According to still further features in the described preferredembodiments the at least one measure comprises carbon dioxideconcentration at a nostril of the subject.

According to still further features in the described preferredembodiments the at least one measure comprises acoustical data beingindicative of leakage near the cuff outside the endotracheal tube.

According to still further features in the described preferredembodiments the measuring comprises filtering out background data fromthe acoustical data.

According to still further features in the described preferredembodiments the background data is characterized by a frequency beingbelow about 1200 Hz.

According to still further features in the described preferredembodiments the measuring comprises calculating frequency differencecharacterizing the acoustical data, the frequency difference beinginduced by the Doppler effect.

According to still further features in the described preferredembodiments the measuring comprises calculating traveling time ofacoustical signals and utilizing the traveling time for determiningfluid flow near the cuff.

According to still further features in the described preferredembodiments the at least one measure comprises pressure data beingindicative of fluid flow near the cuff outside the endotracheal tube.

According to still further features in the described preferredembodiments the at least one measure comprises flow data beingindicative of fluid flow near the cuff outside the endotracheal tube.

According to still further features in the described preferredembodiments the at least one measure comprises optical data beingindicative of presence of secretions near the cuff outside theendotracheal tube.

According to still further features in the described preferredembodiments the at least one measure comprises difference betweeninhaled and exhaled air volumes passing through the endotracheal tube.

According to still further features in the described preferredembodiments the at least one measure comprises electricalcharacteristics of fluid above the cuff outside the endotracheal tube.

According to still further features in the described preferredembodiments the monitoring of the level at least one identifiableadditive is performed above the cuff below the vocal cords of thesubject.

According to still further features in the described preferredembodiments the measuring device comprises a mass spectrometer.According to still further features in the described preferredembodiments the monitoring of the level of the at least one identifiableadditive comprises performing mass spectrometry.

According to still further features in the described preferredembodiments the measuring device comprises a gas analyzer.

According to still further features in the described preferredembodiments the at least one identifiable additive is characterized bymeasurable electric properties. According to still further features inthe described preferred embodiments the measuring device is capable ofmeasuring the electric properties. According to still further featuresin the described preferred embodiments the monitoring of the at leastone identifiable additive is by measuring the electric properties.

According to still further features in the described preferredembodiments the at least one identifiable additive is characterized bymeasurable magnetic properties. According to still further features inthe described preferred embodiments the measuring device is capable ofmeasuring the magnetic properties. According to still further featuresin the described preferred embodiments the monitoring the at least oneidentifiable additive is by measuring the magnetic properties.

According to still further features in the described preferredembodiments the at least one identifiable is characterized by measurableoptical properties. According to still further features in the describedpreferred embodiments the measuring device is capable of measuring theoptical properties. According to still further features in the describedpreferred embodiments the monitoring the at least one identifiableadditive is by measuring the optical properties.

According to still further features in the described preferredembodiments the at least one identifiable is characterized by measurableradiative properties. According to still further features in thedescribed preferred embodiments the measuring device is capable ofmeasuring the radiation properties. According to still further featuresin the described preferred embodiments the monitoring the at least oneidentifiable additive is by measuring the radiation properties.

According to still further features in the described preferredembodiments the at least one identifiable is characterized by measurablefluorescent properties. According to still further features in thedescribed preferred embodiments the measuring device is capable ofmeasuring the fluorescent properties. According to still furtherfeatures in the described preferred embodiments the monitoring the atleast one identifiable additive is by measuring the fluorescentproperties.

According to still further features in the described preferredembodiments the at least one identifiable additive comprises at leastone inert gas. According to still further features in the describedpreferred embodiments the at least one inert gas is selected from thegroup consisting of comprises helium and krypton.

According to still further features in the described preferredembodiments the at least one identifiable additive comprises at leastone colored gas.

According to still further features in the described preferredembodiments the at least one identifiable additive comprises at leastone radioisotope. According to still further features in the describedpreferred embodiments the at least one radioisotope is selected from thegroup consisting of a technetium radioisotope, a xenon radioisotope anda krypton radioisotope.

The present invention successfully addresses the shortcomings of thepresently known configurations by providing a system and method forperforming endotracheal intubation and optimizing endotracheal tube cufffilling.

Unless otherwise defined, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention belongs. Although methods and materialssimilar or equivalent to those described herein can be used in thepractice or testing of the present invention, suitable methods andmaterials are described below. In case of conflict, the patentspecification, including definitions, will control. In addition, thematerials, methods, and examples are illustrative only and not intendedto be limiting.

Implementation of the method and system of the present inventioninvolves performing or completing selected tasks or steps manually,automatically, or a combination thereof. Moreover, according to actualinstrumentation and equipment of preferred embodiments of the method andsystem of the present invention, several selected steps could beimplemented by hardware or by software on any operating system of anyfirmware or a combination thereof. For example, as hardware, selectedsteps of the invention could be implemented as a chip or a circuit. Assoftware, selected steps of the invention could be implemented as aplurality of software instructions being executed by a computer usingany suitable operating system. In any case, selected steps of the methodand system of the invention could be described as being performed by adata processor, such as a computing platform for executing a pluralityof instructions.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

The invention is herein described, by way of example only, withreference to the accompanying drawings. With specific reference now tothe drawings in detail, it is stressed that the particulars shown are byway of example and for purposes of illustrative discussion of thepreferred embodiments of the present invention only, and are presentedin the cause of providing what is believed to be the most useful andreadily understood description of the principles and conceptual aspectsof the invention. In this regard, no attempt is made to show structuraldetails of the invention in more detail than is necessary for afundamental understanding of the invention, the description taken withthe drawings making apparent to those skilled in the art how the severalforms of the invention may be embodied in practice.

In the drawings:

FIG. 1 is a schematic illustration of a prior art intubation system;

FIG. 2 is a schematic illustration of an endotracheal tube cuff duringinhalation and exhalation;

FIGS. 3 a-c are flowchart diagrams of a method suitable for intubating asubject, according to various exemplary embodiments of the presentinvention;

FIGS. 4 a-b show partial CO₂ pressure at different measuring locations,in various exemplary embodiments of the invention;

FIGS. 5 a-b are schematic illustrations of the location of an acousticalmeasuring device, according to various exemplary embodiments of thepresent invention;

FIG. 5 c shows a representative example of a procedure for identifyingleakage by the Doppler effect, according to various exemplaryembodiments of the present invention;

FIG. 5 d shows the difference between the functional dependences of thepressure in the lungs and the pressure in a leaking duct during abreathing cycle, according to various exemplary embodiments of thepresent invention;

FIGS. 6 a-b are schematic illustrations of the flow of air (FIG. 6 a)and the pressure (FIG. 6 b), in the trachea outside the endotrachealtube;

FIGS. 7 a-c are flowchart diagrams of another method suitable forintubating a subject, according to various exemplary embodiments of thepresent invention;

FIG. 8 is a simplified illustration of a system for intubating asubject, according to various exemplary embodiments of the presentinvention;

FIGS. 9 a-b are simplified illustrations of another system forintubating a subject, according to various exemplary embodiments of thepresent invention.

FIG. 10 shows the anatomic locations of CO₂ sampling performed accordingto the teaching of the present invention, in a human simulator and inpatients under general anesthesia;

FIG. 11 shows exhaled CO₂ pressure waveform in accordance withendotracheal tube cuff pressures as displayed during an experimentperformed according to the teaching of the present invention;

FIG. 12 shows the correlation between endotracheal tube cuff pressuresand CO₂ levels measured between the cuff and the vocal cords, during anexperiment performed according to the teaching of the present invention;

FIGS. 13 a-b show correlation between endotracheal tube cuff pressureand upper airway CO2 levels in two porcine models;

FIG. 14 shows comparison between the initial mean endotracheal tube cuffpressure, determined clinically by a anesthesiologist using the audibleleakage test and exhalation-inhalation volume difference, to the meanoptimal cuff pressure determined by CO2 leakage monitoring (n=60); and

FIG. 15 shows percentage of patients with initial endotracheal tube cuffpressure significantly higher, lower, or accurate compared to theoptimal cuff pressure determined by PCO₂ leakage monitoring (n=60).

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present embodiments comprise a method and system which can be usedfor intubation. Specifically, the present invention can be used foroptimizing endotracheal tube cuff filling.

For purposes of better understanding the present invention, asillustrated in FIGS. 2-15 of the drawings, reference is first made tothe construction and operation of a conventional (i.e., prior art)intubation system as illustrated in FIG. 1.

Before explaining at least one embodiment of the invention in detail, itis to be understood that the invention is not limited in its applicationto the details of construction and the arrangement of the components setforth in the following description or illustrated in the drawings. Theinvention is capable of other embodiments or of being practiced orcarried out in various ways. Also, it is to be understood that thephraseology and terminology employed herein is for the purpose ofdescription and should not be regarded as limiting.

Referring now to the drawings, FIG. 1 illustrates a prior art intubationsystem invented by the same inventor as the present invention, generallyreferred to herein as system 1. System 1 comprises an endotracheal tube10 which is inserted into a patient airway. An inflatable cuff 12 isassociated with tube 10 and arranged to be located at a location in thepatient airway 11 below the vocal cords 13. Tube 10 is coupled to aventilator 114 and the inflatable cuff 12 is connected to a cuffinflator 118, via inflation conduit 116.

System 1 further comprises a carbon dioxide (CO₂) monitor 14 whichmonitors CO₂ concentration in airway 11 at a CO₂ monitoring location 16above cuff 12. Monitor 14 is coupled to location 16 via a CO₂ monitoringconduit 18. Additionally, system 1 comprises a suctioning device 20 forsuctioning secretions at a suctioning location 22 above cuff 12.

Monitor 14 provides an indication of the sealing of airway 11 by cuff 12thereby increases the respiration efficiency and reduces pressurerelated damage to airway 11. The operation of suctioning device 20further improves the intubation process by removing secretions upstreamof cuff 12 so as prevent the secretions from entering airway 11downstream of cuff 12. This prevention is the result of the combinationof effective sealing of airway 11 and removal of secretions upstream ofcuff 12.

The CO₂ serves as an indicator for the leakage of secretions into thelungs. System 1 is therefore directed to the detection of CO₂ above thecuff. Any presence of CO₂ above the cuff is used by system 1 as anindicator for secretions leakage into the lungs.

The performances of system 1 above, however, are not optimal. This isbecause there is no indication whether the airway is sealed under theoptimal conditions. Although the presence of CO₂ above the cuff mayindicate the leakage of secretions into the lunge, it is not always thecase. Due to the viscosity of the secretions in the airway, there aresituations in which the cuff is not completely sealed for passage ofair, and yet there is no leakage of secretions into the lungs. Undersuch conditions, it is desired not to increase the cuff pressure, so asnot to cause pressure related damage to the tissues contacting the cuff.

FIG. 2 illustrate the problems associated with leakage of secretionspast the cuff. Typically, the contact area between the cuff and thetrachea is about 2600-3200 mm² on a generally cylindrical inner wall,about 75-80 mm in perimeter and about 35-40 mm in length. The secretionsleakage begins when open ducts are formed between the cuff and the innerwall of the trachea. The open ducts are formed due to changes intemperature, posture of the subject and the like. These changes aresupplemented by the periodic operation of the breathing or anesthesiamachine. The pressure below the cuff increases to about 780 mm Hg duringinhalation, and decreases to about 760 mm Hg (at sea level) duringexhalation. This periodic process generates relative motion between thecuff and the inner wall of the trachea, resulting in the formation ofthe aforementioned open ducts.

Under such conditions, secretions produced at the subglottis begin topenetrate into small volumes formed between the surfaces of the cuff andthe tracheal wall. The secretions are subjected to several forces:gravity (patient is tilted about 30-45 degrees above to horizontalorientation), external friction (applied by the surfaces of trachealwall and the cuff), internal friction (viscosity of the secretions),pressure difference of about 20 mm Hg during inhalation, capillarity andgravity. The direction of the resulting effective force is typically tothe lungs, resulting in leakage of secretions and potential damage tothe subject.

The situation is aggravated over time because the interaction betweenthe secretions and air passing outside the endotracheal tube, results insolidification of the secretions. Under such circumstances, any smallchange in the posture of the subject increases the leakage of newlyformed secretions into the lungs.

It is therefore the object of the present invention to provide a methodand system which allow the identification of leakage formation at anearly stage so as to timely and optimally adjust the inflation pressureof the cuff. While conceiving the present invention it has beenhypothesized and while reducing the present invention to practice it hasbeen realized that damage to the intubated subject can be significantlyreduced if the intubation system operates under optimal conditions whichare defined prior to the intubation procedure.

Reference is now made to FIGS. 3 a-c which are flowchart diagrams of amethod suitable intubating a subject, according to various exemplaryembodiments of the present invention.

It is to be understood that, unless otherwise defined, the method stepsdescribed hereinbelow can be executed either contemporaneously orsequentially in many combinations or orders of execution. Specifically,the ordering of the flowchart diagrams provided herewith is not to beconsidered as limiting. For example, two or more method steps, appearingin the following description or in a particular flowchart diagram in aparticular order, can be executed in a different order (e.g., a reverseorder) or substantially contemporaneously. Additionally, several methodsteps described below are optional and may not be executed.

The method begins at step 30 and continues to step 31 in which anendotracheal tube is inserted into the airway of the subject. The methodcontinues to step 32 in which a cuff associated with the endotrachealtube is inflated within the airway below the vocal cords of the subject.In various exemplary embodiments of the invention the method continuesto optional step 33 in which secretions are suctioned at a suctioninglocation in the airway above the cuff. In the embodiments in which theoptional suctioning step is executed, it can be performed either in analternating, continuous or contemporaneous manner with any of the othermethod steps described below. For example, step 33 can be performed in acontinuous manner contemporaneously with a sequential execution of steps34-37 or 35-37 described below. Alternatively, step 33 can be executedwhenever the method loops back from step 37.

There are several advantages for executing the suctioning step notcontemporaneously with other steps of the method.

One advantage is that continuous suctioning of secretions can damage themucosal membrane of the subglottis. Intermittent execution of thesuctioning step relieves the continuous load on the tissue.

Another advantage is that time separation between the suctioning stepand the other steps reduces or eliminates the influence of thesuctioning operation on the results of leakage identification. Asfurther explained below, the leakage identification is preferably basedon measurement of one or more measures which are indicative ofsecretions leakage past the cuff into the lungs. When the suctioningoperation is performed contemporaneously with the measuring step, it caninfluence on the measurement by altering the level of theleakage-indicating measure. For example, as will be explained below, inone embodiment, the leakage-indicating measure is a CO₂ concentration orpartial pressure. The execution of the suctioning step notcontemporaneously with the measurement of CO₂ concentration or partiallevel, eliminates the interference between the suctioning and themeasurement, because the concentration or partial pressure of CO₂ is notchanged by the suctioning device during the measurement. Since thesuction power of the suctioning device is typically higher than thepumping power of CO₂, time separation between the suctioning step andthe CO₂ measuring step prevent obstruction of the CO₂ measurement by thesuctioning device.

Furthermore, the execution of the suctioning step prior to themeasurement allows the measurement to be performed in a substantiallysecretions-free environment, thus improving the efficiency and accuracyof the measurement.

According to a preferred embodiment of the present invention theinsertion of the endotracheal tube is accompanied by the insertion ofsuctioning conduit to facilitate the execution of the optionalsuctioning step.

In various exemplary embodiments of the invention the method comprisesan optional step 34 in which ambient CO₂ partial pressure is measured.The measurement is preferably performed in the immediate surroundings ofthe subject. For example, when the intubation is performed in theemergency room, the ambulatory transportation vehicle, the operatingroom and the like. In the embodiment in which step 34 is performed, theambient CO₂ partial pressure is utilized for setting a reference valuefor the measurement or measurements performed in step 35 describedbelow. The ambient CO₂ partial pressure measurement can be performedonce, before or after the insertion of the endotracheal tube into theairway, or, more preferably, in a continuous manner throughout theprocedure, e.g., contemporaneously with step 33. In this embodiment, aseries of real-time values for the ambient CO₂ partial pressure ispreferably provided. Alternatively, the ambient CO₂ partial pressuremeasurement can be performed in an alternating manner with any of themethod steps. For example, the measurement can be performedalternatively with step 35. The reference ambient value can be measuredwhile the system is in suction process. Since the rate of change in theambient CO₂ partial pressure is expected to be low, the ambientmeasurement can be performed, e.g., once per hour or even once per 2hours.

Whether or not the optional steps are executed, the method continues tostep 35 in which a measurement of a measure being indicative of leakageis performed. Many measures are contemplated. Generally, the measure canbe any quantity whose level is in correlation with leakage of secretionspast cuff to the lungs. Measurements of several different measures canalso be performed so as to increase the accuracy of the procedure. Inthis case, all the measures are preferably weighted using apredetermined set of weights which may correspond, for example, to therelative accuracy level of each measure and/or its correlation levelwith the secretions leakage. Typically, but not obligatorily, themeasure can be concentration of CO₂ above cuff or a proxy measure fromwhich such concentration can be inferred. Representative examples ofleakage-indicating measures are provided hereinafter. The measurement isperformed using one or more measuring devices suitable for measuring theselected leakage-indicating measure(s). According to a preferredembodiment of the present invention the insertion of the endotrachealtube is accompanied by the insertion of a communication device (e.g., aconduit) which communicates with the measuring device(s).

The measurement of step 35 is performed at a measurement location whichis accessible to the measuring device or the communication device.Preferably, the measurement location is selected so as to optimize theaccuracy of the measurement while minimizing discomfort to the subject.Thus, for example, the measurement location can be at the nostril of thesubject, between the cuff and the vocal cords, above the vocal cords(e.g., at the oropharynx) and/or below cuff and adjacent thereto.Whereas the nostril or oropharynx are more convenient measurementlocations to the operator and patient, performing the measuring near thecuff is more preferred from the standpoint of the measurement accuracyand analysis reliability.

Once the leakage-indicating measure is obtained the method continues tostep 36 in which the level of the measure is compared with an optimalreference level of the measure. According to a preferred embodiment ofthe present invention the optimal level is predetermined. The optimallevel can also be updated periodically by measuring ambient level, as inthe case of, e.g., CO₂. In the preferred embodiment in whichmeasurements of more than one measure are performed, the level of eachmeasure is preferably compared with a respective optimal referencelevel.

The optimal level is preferably the maximal level of the respectivemeasure which is indicative to a negligibly low or no leakage ofsecretions from above the cuff into the lung. Thus, the optimal levelenacts a leakage identification threshold. As long as the level of themeasure is below the threshold, the leakage is considered negligible (ornonexistent) and the airway is considered properly sealed. The thresholdis typically a lower bound, so that secretions leakage is identified atthe location of the cuff whenever the level of the measure exceeds thethreshold. Alternatively, the threshold can be defined as an upper boundin which case so that secretions leakage is identified at the locationof the cuff whenever the level of the measure is below the threshold.

The optimal reference level can be extracted from studies directed todetermine this level, tables, charts, graphs or formulae obtained byempirical considerations and/or theoretical calculations. For example,in experiments performed by the inventor of the present invention it wasfound that there is a leakage of secretions when the partial pressure ofCO₂ is well above the typical atmospheric CO₂ partial pressure (about0.03%, or about 0.26-0.32 mm Hg).

Thus, in the embodiment in which the leakage-indicating measure ispartial pressure of CO₂, the optimal level of is preferably P mm Hg,where P is a partial pressure which is above the ambient CO₂ partialpressure, P_(ref). P_(ref) can be known in advance (before theintubation procedure), or, more preferably, can be measured during theexecution procedure, as further detailed hereinabove. Denoting by AP the(positive) difference P−P_(ref), ΔP is preferably lower or equal about 4mm Hg, more preferably lower or equal about 2 mm Hg, more preferablylower or equal about 1 mm Hg, even more preferably lower or equal about0.4 mm Hg. For example, assuming a hospital ventilation rate standardsas 40 cubic feet per minute per person (to this end see, e.g.,Air-Conditioning Engineers (ASHRAE) Standard 62-1989 VentilationStandard for Acceptable Air), P can be from about 0.32 mm Hg to about 4mm Hg, more preferably from about 0.32 mm Hg to about 2 mm Hg, morepreferably from about 0.32 mm Hg to about 1 mm Hg, even more preferablyfrom about 0.32 mm Hg to about 0.7 mm Hg.

As used herein the term “about” refers to ±10%.

The leakage-indicating measure can also be a measure other than CO₂concentration. In this embodiment, the leakage-indicating measure ispreferably a proxy measure from which the presence or level of leakagecan be inferred. For example, the leakage-indicating measure can be aproxy measure to CO₂ concentration or CO₂ partial pressure. In thisembodiment, the optimal level can be the level of the proxy measurewhich corresponds to the optimal level of CO₂ concentration or CO₂partial pressure, as further detailed hereinabove.

From the comparison step 36, the method proceeds to step 37 in which theinflation of the cuff is adjusted, based on the comparison to theoptimal level. The adjustment is performed in a manner such that bothleakage of secretion and occurrences of pressure associated damages aregenerally minimized. This is preferably done by reducing the cuffpressure and than raising it gradually to the desired optimal level.Before pressure reduction the suctioning step is preferably executed toclear the space of secretions. From step 37 the method, optionally andpreferably, loops back to step 33 or step 35.

Two alternative and optional execution procedures for step 37 areillustrated in the partial flowcharts of FIGS. 3 b-c. Hence, from step36 (not shown, see FIG. 3 a) the method continues to decision step 37 ain which the method decides whether or not the level of theleakage-indicating measure exceeds the optimal level. If the optimallevel is exceeded, a non-negligible leakage has been identified and themethod continues to process step 37 b in which the inflation pressure ofthe cuff is increased so as to provide better sealing. If optimal levelis not exceeded, the method can either loop back to step 33 or step 35without changing the inflation pressure (FIG. 3 b), or proceed to step37 c in which the inflation pressure of the cuff is decreased (FIG. 3c). From step 37 c the method preferably loops back to step 33 or step35. The advantage of the embodiment of FIG. 3 c is that it allowsfurther optimization of the inflation pressure in the cuff. Theinflation pressure in the cuff can be decreased as long as the leakageis sufficiently low or there is no leakage.

Thus, the method of the present embodiment provides a closed loopcontrol on the inflation of the cuff, such that leakage of secretions isminimized or substantially prevented with a minimal local pressure onthe trachea. Such control facilitates an efficient breathing assistanceto the subject with minimal risk to lung infections or pressure relateddamage to the airway's wall.

The method ends at step 38.

As stated, the leakage-indicating measure can be any quantity whoselevel is in correlation with leakage of secretions past cuff to thelungs. Following are representative examples of leakage-indicatingmeasures which can be measured, in various exemplary embodiments of theinvention.

Hence, in one embodiment, the measure comprises CO₂ concentration orpartial pressure. The measurement can be performed using a CO₂concentration or partial pressure measuring device (e.g., a CO₂analyzer), which can be located in or communicate with a measuringlocation, either between the cuff and the vocal cords, preferably closeto the cuff, or at another location, such as, but not limited to, abovethe vocal cords (e.g., the oropharynx) or at the nostril. For CO₂concentration, the optimal predetermined level (leakage identificationthreshold) can be, as stated, a CO₂ partial pressure which is above theambient CO₂ partial pressure (e.g., from about 0.32 mm Hg to about 4 mmHg). More specific values for the optimal predetermined level can bedefined based on the location at which the CO₂ concentration or partialpressure is measured.

Reference is now made to FIGS. 4 a-b, which show the partial CO₂pressure, denoted PCO₂, at different measuring locations. The solid anddash lines in FIG. 4 b represent partial CO₂ pressure gradients, fordifferent leaking duct diameters. The partial CO₂ pressure exhaled ofthe lungs is typically 30-40 mm Hg (in a healthy person), while theambient partial CO₂ pressure is about 0.26-0.32 mm Hg. As shown in FIG.4 b, there are different pressure drops between different locationsalong the path starting from the cuff and ending at the ambientenvironment (as function of the leaking the volumetric leaking rate).Along the leaking duct, formed between the cuff and the tracheal wall,the partial CO₂, the pressure drops from about 40 mm Hg at the lung toabout 2 mm Hg at the opposite side of the cuff (solid line); along thesubglottis, the pressure drops from about 2 mm Hg near the cuff to about1 mm Hg at the vocal cords; within the pharynx, the pressure dropsfurther to the ambient pressure.

Thus, when the measuring location is near the cuff (between the cuff andthe vocal cords) the optimal predetermined level can be from about 0.32mm Hg to about 4 mm Hg, and when the measuring location above the vocalcords or at the nostril the optimal predetermined level can be fromabout 0.32 to about 1 mm Hg. Other values are also contemplated.

The measurement of partial CO₂ pressure is preferably performed using ameasuring device having a wide dynamic range. More preferably themeasuring device of the present embodiments combines a high-sensitivityCO₂ sensor having a narrow dynamic range with a low-sensitivity CO₂sensor having a wide dynamic range. For example, the high-sensitivityCO₂ sensor can have a sensitivity of about 0.02 mmHg and a dynamic rangeof about 0-1 mm Hg, and the low-sensitivity CO₂ sensor can have asensitivity of about 0.1 mmHg and a dynamic range of about 1-10 mm Hg.When the measurement is performed above the vocal cords or at thenostril, the dynamic range of the measuring device can be lower (e.g.,0-1 mm Hg) with and the accuracy can be higher (e.g., 0.01 mm Hg).

In another embodiment, the measure comprises acoustical data beingindicative of leakage near the cuff outside the endotracheal tube. Theacoustical data can be collected using an acoustical measuring device,which can be positioned, for example, above and/or below the cuffadjacent to the leaking duct. Acoustical measuring devices suitable tobe introduced into the trachea are known in the art and found, e.g., inU.S. Pat. Nos. 5,655,518, 5,890,488, 6,168,568, 6,261,238 and 6,383,142,the contents of which are hereby incorporated by reference.

The ability to identify the formation of a leaking duct using acousticaldevice is attributed to the unidirectional flow of air through the duct.The airflow through the leaking duct is unidirectional from thefollowing reason. During the breathing cycle, the air pressure withinthe lungs is changed periodically. In the inhalation stage, thebreathing machine increases the air pressure in the lungs and a pressuredrop of about 20 mm Hg is built between the lungs and the subglottis.This pressure drop results in airflow from the lungs to the subglottisthrough the leaking duct. On the exit from duct the air expands with thevolume of the subglottis. This expansion continues throughout theinhaling stage.

The magnitude of the air flow through the duct varies from zero (whenthe air pressure in the lungs equals the ambient air pressure) to amaximal value (when the air pressure in the lungs is maximal, e.g.,about 20 mm Hg above ambient air pressure). The maximal magnitude offlow depends on the cross-sectional area of the duct. FIGS. 5 a-b areschematic illustrations of the location of an acoustical measuringdevice 58, according to a preferred embodiment of the present invention.Shown in FIG. 5 a is a trachea 56, an endotracheal tube 54 positionedwithin trachea 56 and a cuff 52 inflated between the external wall oftube 54 and the internal wall of trachea 56. Acoustical measuring device58 preferably comprises a downstream sensor M2 and an upstream sensorM1. Sensors M1 and M2 serve for sensing sound waves impinging thereon.Being spaced apart from each other, the acoustical data collected byeach sensor port is different, inter alia, due to different relativeflow direction (outgoing with respect to sensor M1 and incoming withrespect to sensor M2), as further explained hereinunder. The differencein acoustical data can be used to improve the sensitivity of device 58,as further detailed hereinbelow with reference to FIG. 5 b.

When leakage exists between sensors M1 and M2, due to the differentrelative flow direction and in accordance with the well-known Dopplereffect, the acoustical signal sensed by sensor M2 has a higher frequencycompared to the acoustical signal sensed by sensor M1. Thus, definingthe frequency difference between the acoustical signals sensed by M1 andM2 by Δf=f₂−f₁, where f₁ is the frequency sensed by M1 and f₂ is thefrequency sensed by M2, a leakage can be identified when Δf is higherthan about 20 Hz. A representative example of leakage identification byDoppler effect is shown in FIG. 5 c.

An additional method for identifying leakage is based on the travelingtime of the acoustic sound from sensor M1 to sensor M2.

Air coming out of the lungs through the leaking duct accelerates by theinfluence of the pressure in the lungs. The acoustic signal arrives tosensor M1 at a velocity, v₁, which is the difference between thevelocity of sound, v_(a) (about 340 m/s), and the velocity of the airflowing in the leaking duct, v_(L):

v ₁ =v _(a) −v _(L).  (EQ. 1)

The acoustic signal arrives to sensor M2 at a velocity, v₂, which is thesum of v_(a) and v_(L):

v ₂ =V _(a) +V _(L).  (EQ. 2)

The distances between the source of the acoustical signal and sensors M1and M2 are denoted d₁ and d₂, respectively. The traveling times of theacoustic signal to M1 and M2 are, therefore, t_(i)=d_(i)/v_(i) andt₂=d₂/v₂, respectively. In the following, for the purpose of simplicity,d₁ and d₂ are assumed to be equal,

d _(i) =d ₂ ≡d.  (EQ. 3)

The difference in the traveling times is a measurable quantity. Denotingthis difference by Δt one obtains from Equations 1-3:

Δt=d/(v _(a) −v _(L))−d/(v _(a) +V _(L)),  (EQ. 4)

or

Δt=2d v ₁/(v _(a) −v _(L))(v _(a) +V _(L))≈2d v _(L) /v _(a) ²  (EQ. 5)

where in the last step, the square of the v_(L) was neglected comparedto the square of the V_(a).

As can be understood from Equation 5 above, knowing the value of Δt, dand v_(a), the value of V_(L), hence also the presence of leakage, canbe identified. Thus, according to the presently preferred embodiment ofthe invention the leakage-indicating measure is in correlation with thevelocity, V_(L). In this embodiment, the optimal level preferablycorresponds to a velocity of from about 1 m/s to about 3 m/s.

The measurement of acoustical data is preferably performed such thatbackground noise is filtered out. The background noise can include allacoustical data associated with phenomena other than leakage of fluidthrough the leaking duct. Most of the background noise is generated bythe breathing machine. During the exhalation stage of the machine(inhalation stage of the subject), the flow in a direction which isopposite to the unidirectional flow through the leaking duct. This isbecause the air expands, between the cuff and the lungs, from the lowdiameter of endotracheal tube to the larger diameter of the trachea.During the inhalation stage of the machine (exhalation stage of thesubject), the air is compressed again. Thus, the background noise ischaracterized by oscillatory behavior (from compression to expansion andvise verse) whereas the flow through the leaking duct is unidirectional.The difference between the functional dependences of the pressure in thelungs and the pressure in the leaking duct during the breathing cycle isshown in FIG. 5 d.

The filtering of the background noise can be done by spectral analysisof the collected acoustical data. Generally, acoustical datacharacterized by frequencies of from about 1200 Hz to about 2500 Hz, canbe identified as proxy to the leakage. Other acoustical data can beassociated with breathing, berating disorders, hoarseness and motion ofmuscles, such as the heart and lungs. Although acoustical dataassociated with breathing typically includes low frequencies (below 300Hz), intermediate frequencies (between 300 and 600 Hz) and highfrequencies (between 600 and 1200 Hz), most of the breathing energy isat the range of 60-600 Hz. Acoustical data associated with motion of theheart and lungs is typically in the low frequencies. Acoustical dataassociated with berating disorders or hoarseness are typically above the2000 Hz.

The identification of acoustical data to be excluded can also beperformed by performing a calibration step in which the acousticalmeasurements are performed sufficiently far from the leaking duct so asto define the background noise. Once the background noise is defined itcan be subtracted from data collected near the cuff.

In an additional embodiment, the leakage-indicating measure comprisespressure data being indicative of fluid flow near the cuff outsideendotracheal tube. Pressure data can be measured using a pressuremeasuring device.

FIGS. 6 a-b are schematic illustrations of the flow of air (FIG. 6 a)and the pressure (FIG. 6 b), in the trachea outside the endotrachealtube. The stagnation pressure in the lung during the inhalation stage isabout 780 mm Hg, which, as stated, is about 20 mm Hg above the ambientpressure. The air flowing through the leaking duct enters the subglottisin turbulent flow. By the time the air reach the end of the subglottis(near the vocal cords) the flow becomes laminar.

Thus, according to a preferred embodiment of the present invention thepressure is measured at the pressure measuring location within thesubglottis. The location is preferably near the vocal cords, where theairflow is substantially laminar. The air pressure, P_(sd), at thepressure measuring location decreases according to the equation:

P _(sd)=(P _(LT) −P _(a))(A _(d) /A _(s)),  (EQ. 6)

where, P_(LT) is the dynamic pressure near the leaking duct (on theentry to the subglottis), P_(a) is the ambient pressure, A_(d) is thecross sectional area of the leaking duct (on the entry to thesubglottis) and A_(s) is the cross sectional area of the subglottis atthe pressure measuring location.

As a representative numerical example, when the diameter of the tracheais about 15-30 mm, the inner diameter of the endotracheal duct is about7-8.5 mm and the cross sectional area of the leaking duct is about 5-25mm², P_(sd) is from about 0.01 to about 2 mm Hg. Thus, according to apreferred embodiment of the present invention the pressure measuringdevice is characterized by a dynamic range of about 0-2 mm Hg andresolution of 0.01 mm Hg.

Miniature sensitive pressure measuring devices are known in the art.Representative example of suitable pressure measuring devices includethe pressure sensors of Nexense™, Israel, described, e.g., in U.S. Pat.Nos. 6,621,278 and 6,856,141, International Publication Nos. WO00/67013, WO 03/036321, WO 03/048688, WO 2004/072658, WO 2005/062719,and WO2005/076727, and U.S. Patent Application Nos. 20050027206,20040207409, 20040104733, and 20020105340, the contents of which arehereby incorporated by reference.

In an additional embodiment, the leakage-indicating measure comprisesflow data being indicative of fluid flow near the cuff outsideendotracheal tube. Flow data can be measured using a flow measuringdevice, such as a flow meter. The flow measuring device is preferablylocated near the cuff within the subglottis, such that when air flowsfrom the lungs through the leakage duct, the flow measuring devicemeasures the flow. According to a preferred embodiment of the presentinvention the flow measuring device is characterized by a dynamic rangeof about 1-3 m/s and resolution of about 10%. Miniature sensitive flowmeasuring devices are manufactured by Nexense™, Israel, and described inthe aforementioned patents and patent applications.

In still another embodiment, the leakage-indicating measure comprisesoptical data being indicative of presence of secretions near the cuffoutside endotracheal tube. In this embodiment, the measuring devicecomprises one or more miniature cameras located below the cuff, betweenthe cuff and the lung. The cameras capture images, preferably videoimages, which can be analyzed to identify leakage of secretions throughthe leaking duct in the direction of the lungs. Mature cameras which canbe mounted on an endotracheal tube are known in the art, (see, e.g.,MedGadget Journal, March 2005 issue,http://www.medgadget.com/archives/2005/03/etview_ett.html)

In yet another embodiment, the leakage-indicating measure comprisesdifference between inhaled and exhaled air volumes passing through theendotracheal tube. In this embodiment, the measurement can be performedat the inlet of the breathing machine. The amount of inhaled and exhaledair volume is recorded and the difference therebetween is calculated.Based on this difference, the identification of leakage is achieved.

In a further embodiment, the leakage-indicating measure compriseselectrical characteristics of fluid above the cuff outside endotrachealtube. In this embodiment, the fluid above the cuff is transferred into achamber where it is being heated. When the air contains CO₂ it becomeselectrically conductive at high temperatures. The electricalconductivity thus serves as a proxy measure to the concentration of CO₂above the cuff. According to a preferred embodiment of the presentinvention a leakage is identified whenever the electrical conductivityof the air above the cuff exceeds an optimal level. The optimal levelcan correspond to the aforementioned partial CO₂ pressure levels.

Reference is now made to FIGS. 7 a-c which are flowchart diagrams of amethod suitable intubating a subject, in preferred embodiments in whichthe leakage is identified by delivering additives to the subject.

The method begins at step 370 and continues to steps 31 and 32 asdescribed hereinabove. The method can also continue to the optionalsuctioning step 33 as described hereinabove. The optional suctioningstep can be performed in an intermittent, continuous or contemporaneousmanner with any of the other method steps described below. Morespecifically, step 33 can be performed in a continuous mannercontemporaneously with a sequential execution of steps 374-377 or375-377 described below. Alternatively, step 33 can be executed wheneverthe method loops back from step 377.

The method continues to step 374 in which a breathing gas and one ormore identifiable additives are delivered through the endotracheal tube.The breathing gas can be any breathing gas typically delivered tosubjects from a conventional breathing or anesthesia machine, such as,but not limited to, air, filtered air, enriched air, a mixture of airand one or more anesthetic agents, and the like. The identifiableadditive is preferably in fluid form (e.g., gaseous form) and it can beeither mixed with the breathing gas prior to the delivery or it can bedelivered from a different container. Being designed to enter the bodyof the subject, the identifiable additive is preferably of low toxicityor, more preferably non toxic.

The delivery of the additive is preferably performed so as to allow theadditive to enter the lungs of the subject. During the breathing cycle,additive remnants pass through the lungs and, together with the carbondioxide waste, are expelled from the lungs by the breathing machine.Alternatively, the additive can be delivered to a location above thecuff, between the airway's wall and the endotracheal tube. In thisembodiment, the additive only enters the lungs when there is a leakingduct between the cuff and the airway.

The delivery of the additive can be performed continuously throughoutthe procedure or at predetermined time intervals (e.g., whenever themethod loops back to step 33 or step 374, as further detailedhereinafter). In the embodiment in which the additive is delivered to alocation above the cuff, the delivery can be executed once for theentire procedure, or whenever the level of the additive at the locationabove the cuff decreases to below a predetermined threshold.

Many types of identifiable additives are contemplated. Broadly speaking,for the additive to be identifiable, it should have at least onemeasurable property which can be used for distinguishing the additivefrom the breathing gas or other materials in the environment. Thus, theadditive is preferably absent from the environment or present inenvironment in low and known concentrations. When the additive isalready present in the environment, it is preferably delivered at asufficiently higher concentration so as to allow identifying theadditive by its concentration level. The distinguishing property of theadditive can be, for example, atomic mass, molecular mass and/or one ormore other distinguishable properties, including optical, fluorescentand radiative properties. Additionally or alternatively, the additivecan have specific electric and/or magnetic properties which can be usedto identify the additive.

Representative examples of identifiable additives suitable for thepresent embodiments include, without limitation, inert gases such ashelium, krypton, etc.; radioisotopes, preferably low-radiationradioisotopes with sufficiently short half lives (several seconds toseveral days) such as technetium radioisotope (e.g., Tc-99), xenonradioisotope (e.g., Xe-133), krypton radioisotope (e.g., Kr-81); coloredgases, preferably non-toxic colored gases; and various fluorescentmaterials, preferably non-toxic fluorescent materials.

The amount of additive which is delivered is preferably selectedsufficiently high to allow its identification and sufficiently low so asnot to interfere with the breathing of the subject or cause damage toliving tissue. The amount can be selected in accordance with the FDAregulations of the specific type of additive used. The optimal amountthus depends on the type of additive and the measuring device whichidentifies it. It was found by the present inventors that additivessuitable for the present embodiments can be identified with an accuracyof from about 7.5×10⁻¹² (e.g., via mass spectrometry) to about 0.001(e.g., via radiation detection). Thus, the ratio between the volume ofadditive to the volume of inhaled air is preferably less than R, where Ris a number from about 7.5×10⁻¹² to about 0.001. Where the lower limitis applicable to detection via mass spectrometry.

As used herein, “about” refers to ±10% (e.g., “about 7.5×10⁻¹²” refersto the range 6.75×10⁻¹²-8.25×10⁻¹², while “about 0.001” refers to therange 0.0009-0.0011).

The method continues to step 375 in which the level of the identifiableadditive is monitored. The monitoring is performed so as to identifyleakage of the additive past the cuff towards the vocal cords. As willbe appreciated by one of ordinary skill in the art, the identificationof such leakage is a proxy to the formation of a leaking duct betweenthe cuff and the airway's inner wall, which formation is typicallyaccompanied by secretions past cuff to the lungs.

In various exemplary embodiments of the invention the monitoring isperformed in a substantially continuous manner throughout the intubatingprocedure. This can be done, for example, by obtaining a series ofreal-time values for the level of the additive. In the embodiments inwhich more than one additive is delivered through the endotracheal tube,the monitoring preferably comprises measurements for more the level ofmore than one additive, more preferably all the delivered additives. Inthis case, all the measures are preferably weighted using apredetermined set of weights which may correspond, for example, to therelative accuracy level of each measurement and/or its correlation levelwith the secretions leakage.

The monitoring can be performed using one or more measuring devicessuitable for measuring the distinguishing property of the additive.According to a preferred embodiment of the present invention theinsertion of the endotracheal tube is accompanied by the insertion of acommunication device (e.g., a conduit) which communicates with themeasuring device(s). The conduit can be disposed externally to theendotracheal tube or it can be embedded in the wall of the tube, asfurther detailed hereinafter.

The monitoring is performed at a monitoring location which is accessibleto the measuring device or the communication device. In variousexemplary embodiments of the invention the monitoring is done bysampling fluids (gas or liquid) from the monitoring location anddelivering the sample to the measuring device for analysis. Preferably,the monitoring location is selected so as to optimize the accuracy ofthe measurement while minimizing discomfort to the subject. Suitablemonitoring locations include, without limitation, above the cuff betweenthe endotracheal tube and the walls of the airway, at the nostril of thesubject or above the vocal cords (e.g., at the oropharynx) and/or belowcuff and adjacent thereto. Whereas the nostril or oropharynx are moreconvenient measurement locations to the operator and patient, performingthe measuring near the cuff is more preferred from the standpoint of themeasurement accuracy and analysis reliability. When the additive isdelivered to a location above the cuff, the monitoring location can bebelow the cuff, in the lungs, or in the breathing lumen of theendotracheal tube near or at the ventilator.

According to a preferred embodiment of the present invention themeasurements are performed by a mass spectrometer or a gas analyzer,which can provide information regarding the composition and abundance ofthe atoms present between the airway's wall and the endotracheal tube,thereby to identify additive and to measure its level. For example, whenthe additive comprises an inert gas (e.g., helium, krypton) the massspectrometer can identify presence of the atoms of the inert gas (e.g.,He, Kr) and optionally measure their concentration level. Other gaseousmaterials can also be identified using mass spectrometer.

In another embodiment, the measurements are performed by a radiationdetecting device. This embodiment is preferred when the additive hasspecific radiative properties. For example, when the additive comprisesradioisotope (e.g., Tc-99, Xe-133, Kr-81), the radiation detectingdevice can detect radiation emitted by the radioisotope and the presenceand/or concentration level of the radioisotope in the between theairway's wall and the endotracheal tube can thus be determined. This canbe achieved by sampling fluids (gas or liquid) from the monitoringlocation and delivering the sample to the radiation detecting device.

An additional embodiment is preferred when the additive has adistinguishing optical property. In this embodiment the measurements areperformed by an optical device capable of measuring the opticalproperty. For example, the optical property of the additive can be adistinct color (such as, for example, in the case of colored gas), inwhich case the optical device can include a miniature camera or anoptical waveguide coupled to an external camera. Miniature camerasmountable on an endotracheal tube are known in the art, (see, e.g.,MedGadget Journal, March 2005 issue,http://www.medgadget.com/archives/2005/03/etview_ett.html).

Images captured by the camera can be processed to detect the presence ofthe additive and optionally determine its concentration level above thecuff. The optical property of the additive can also be fluorescence, inwhich case the optical device can be a fluorescence camera for detectingfluorescent emissions from the additive, thereby enabling the presencedetection and/or concentration level measurement of the additive. Whenthe additive is delivered to a location above the cuff, images arepreferably captured below the cuff so as to identify leakage once theadditive passes the cuff downstream to the lungs. In this embodiment,the additive can also be selected such that its passing through theleaking duct is accompanied by the formation of colored or colorlessbubbles which can be detected by the camera. Bubbles can be alsodetected by a miniature ultrasound device.

An additional embodiment is preferred when the additive has adistinguishing electrical property. In this embodiment the measurementsare performed by a device capable of measuring electrical properties,such as conduction or resistance. Alternatively or additionally, whenthe additive has a distinguishing magnetic property, the measurementsare performed by a device capable of measuring magnetic properties,e.g., magnetization. Thus, measurements of the respective quantity canbe performed substantially continuously in the monitoring location so asto determine presence or concentration level of the additive above thecuff.

Once the measurements are performed the method preferably continues tostep 376 in which the level of the identifiable additive is comparedwith an optimal level thereof, which is preferably predetermined. In thepreferred embodiment in which more than one additive is used, the levelof each identifiable additive is preferably compared with a respectiveoptimal level.

The optimal level is preferably the maximal level of the respectiveadditive which is indicative to a negligibly low or no leakage ofsecretions from above the cuff into the lung. Thus, the optimal levelenacts a leakage identification threshold. As long as the level of theadditive is below the threshold, the leakage is considered negligible(or nonexistent) and the airway is considered properly sealed. Thethreshold is typically a lower bound, so that secretions leakage isidentified at the location of the cuff whenever the level of theadditive exceeds the threshold.

The optimal level can be an absolute optimal level or it can be definedrelative to an online reference of, e.g., ambient or breathing gas. Theoptimal level can be extracted from studies directed to determine thislevel, tables, charts, graphs or formulae obtained by empiricalconsiderations and/or theoretical calculations.

According to a preferred embodiment of the present invention the methodproceeds to step 377 in which the inflation of the cuff is adjusted,based on the level of the identifiable additive. The adjustment isperformed in a manner such that both leakage of secretion andoccurrences of pressure associated damages are generally minimized. Fromstep 377 the method, optionally and preferably, loops back to step 33,374 or 375.

Two alternative and optional execution procedures for step 377 areillustrated in the partial flowcharts of FIGS. 7 b-c. Hence, from step376 (not shown, see FIG. 7 a) the method continues to decision step 377a in which the method decides whether or not a non-negligible leakage isidentified, based, as stated on the level of the additive. Ifnon-negligible leakage is identified the method continues to processstep 377 b in which the inflation pressure of the cuff is increased soas to provide better sealing. If the method decides that there is noleakage (or that the leakage is negligible), the method can either loopback to step 373, 374 or 375 without changing the inflation pressure(FIG. 7 b), or proceed to step 377 c in which the inflation pressure ofthe cuff is decreased (FIG. 7 c). From step 377 c the method preferablyloops back to step 373, 374 or 375. The advantage of the embodiment ofFIG. 7 c is that it allows further optimization of the inflationpressure in the cuff. The inflation pressure in the cuff can bedecreased as long as the leakage is sufficiently low or there is noleakage.

Thus, the method of the present embodiment provides a closed loopcontrol on the inflation of the cuff, such that leakage of secretions isminimized or substantially prevented with a minimal local pressure onthe trachea. Such control facilitates an efficient breathing assistanceto the subject with minimal risk to lung infections or pressure relateddamage to the airway's wall.

The method ends at step 378.

Reference is now made to FIG. 8 which is a simplified illustration of asystem 70 for intubating a subject, according to various exemplaryembodiments of the present invention. System 70 comprises anendotracheal tube 72, adapted to be inserted into the airway 74.Endotracheal tube 72 is associated with a cuff 76 capable of beinginflated, for example, via an inflation conduit 77 below the vocal cordsof the subject (not shown, see, e.g., FIGS. 4 a and 6 a). System 70further comprises a measuring device 78, for measuring at least onemeasure which is indicative of secretion leakage as further detailedhereinabove. In various exemplary embodiments of the invention device 78performs measurements to measures directly related to CO₂(concentration, partial pressure) or proxy measures to CO₂. It isexpected that during the life of this patent many relevant measuringdevices suitable for measuring proxy measures to CO₂ will be developedand the scope of the term measuring devices is intended to include allsuch new technologies a priori.

Device 78 can be, for example, a CO₂ concentration measuring device, aCO₂ partial pressure measuring device, an acoustic measuring device, apressure measuring device, a flow measuring device, an optical measuringdevice (e.g., a camera), a gas-volume measuring device, an electricalcharacteristics measuring device.

In the embodiments in which ambient CO₂ partial pressure is measured,device 78 is preferably capable of performing two parallel measurements,for example, using two or more separate inlets 79 and an arrangement ofunidirectional valves 81. Inlet 79 can also be used for measuringambient measure (e.g., CO₂ partial pressure) to be used as a referencemeasure.

Device 78 can comprise, or be associated with a data processing unit 94which process or analyze the data corresponding to the measuredquantities. For example, can convert the measured quantities to digitaldata and transfer the data to unit 94 for further processing, such as,but not limited to, the analysis of data corresponding to acousticalmeasurements (e.g., filtration of background data or calculation of Δf,Δt or v_(L), as further detailed hereinabove) or the analysis of datacorresponding to optical measurements. Unit 94 can also performcomparison, preferably in real-time, between the level of the measureand its corresponding optimal value. For example, in various exemplaryembodiments of the invention, unit 94 performs real-time comparisonbetween the CO₂ partial pressure near the cuff and the ambient CO₂partial pressure.

Depending on the type of the measuring device, the device can be locatedat the desired measuring location 82, or more preferably it cancommunicate with the measuring location, for example, using a measuringconduit 80. It is to be understood that although FIG. 8 shows measuringlocation 82 above cuff 76, this need not necessarily be the case, since,as stated, it may not be necessary for the measuring location to beabove the cuff, as further detailed hereinabove.

Device 78 can also comprise one or more sensors 84 located at themeasuring location and configured to communicate with device 78 via acommunication channel, such as, but not limited to, measuring conduit80, which can be or include a suitable transmission line. The type ofsensors depends on the type of the measuring device. For example, whenthe measuring device is an acoustical measuring device, the sensors areacoustical sensors, when the measuring device is a pressure measuringdevice the sensors are pressure sensors and the like.

According to a preferred embodiment of the present invention system 70comprises a suctioning device 86 for suctioning secretions at asuctioning location 87 in the airway above cuff 76. Suctioning device 86can be in fluid communication with suctioning location 87 either by asuctioning conduit 88, extending from device 86 to location 87, or byconduit 80, in which case conduit 80 serves as a suctioning andmeasuring conduit. Conduit 80 and/or conduit 88 can be disposed eitherinternally within the endotracheal tube or externally thereto, asdesired. Conduits 80 and/or 88 can also be embedded in wall 63 of tube72.

In various exemplary embodiments of the invention system 70 comprises aninflating device 90 for adjusting the inflation of cuff 76 based onsignals received from device 78. This can be done either manually, bythe operator, in which case the measuring device comprises a displaydevice for displaying the level of the measure, or automatically, inwhich case the inflating device is in communication with the measuringdevice, thereby forming therewith a closed loop control.

System 70 can also comprise an alerting unit 92 which communicates withmeasuring device 78. Unit 92 serves for producing an alert when thelevel of the measure exceeds the optimal level.

Reference is now made to FIGS. 9 a-b which is a simplified illustrationof a system 100 for intubating a subject, according to various exemplaryembodiments of the present invention. Similarly to system 70 above,system 100 preferably comprises endotracheal tube 72, cuff 76 andinflation conduit 77 as further detailed hereinabove. In variousexemplary embodiments of the invention system 100 further comprises anadditive delivering unit 75 which delivers one or more identifiableadditive(s) through the endotracheal tube, as further detailedhereinabove. Unit 75 is thus operatively associated with tube 72. Thisassociation can be via the breathing or anesthesia machine (not shown),in which case unit 75 is preferably a part of, or being in fluidcommunication with, the machine such that the additive is mixed with thebreathing gas prior to the delivery of the additive through tube 72.

Alternatively, unit 75 can be a fluid communication with tube 72, inwhich case the additive is delivered directly from unit 75 to tube 72.When it is desired to allow the additive to enter the lungs 102 of thesubject, the additive and the breathing gas are preferably deliveredthrough the breathing lumen 65 of tube 72. In this embodiment, theadditive and the breathing gas can be allowed to mix. When it is desiredto deliver the additive to a location above the cuff, the additive ispreferably delivered through an additive delivery conduit 71 which caninclude an opening 73 above cuff 76 (see FIG. 9 b). Conduit 71 can bedisposed within the lumen 65 of tube 72 or being adjacent thereto.Conduit 71 can also be embedded in the wall 63 of tube 72. Preferably,but not obligatorily, lumen 65 and conduit 71 are devoid fluidcommunications thereamongst. Also contemplated are asymmetricalconfigurations employing unidirectional valves, in which the additive isprevented from entering lumen 65 but the breathing gas is allowed toenter conduit 71 or vise versa. In the embodiments in which the additiveis delivered through lumen 65, conduit 71 can be used as a measuringconduit 80, as further detailed hereinbelow.

System 100 further comprises a measuring device 85, for measuring thelevel of the identifiable additive(s) as further detailed hereinabove.Device 85 preferably communicates with a monitoring location 83 which,as stated, can be above the cuff, at the nostril of the subject or abovethe vocal cords (e.g., at the oropharynx) and/or below the cuff andadjacent thereto. In the embodiment shown in FIG. 9 a monitoringlocation 83 is above the cuff between the endotracheal tube and thewalls of the airway.

Device 85 can measure one or more of the aforementioned distinguishingproperties of the additive. Thus, device 85 can be, for example, a massspectrometer, a gas analyzer, an optical measuring device (e.g., anoptical camera or a fluorescence camera), a miniature ultrasound device,electrical characteristics measuring device (e.g., a conductionmeasuring device, a resistance measuring device) and a magneticcharacteristics measuring device (e.g., magnetization measuring device).Device 85 can also be a combination of several devices, each designedand constructed to measure a different quantity. For example, device 85can include a mass spectrometer and a camera or any other combination.

Device 85 is preferably capable of performing two parallel measurements,for example, using two or more separate inlets 79 and an arrangement ofunidirectional valves 81. This embodiment is particularly useful when itis desired to determine the level of the additive in the environment,for example for comparing the level of the additive at the monitoringlocation with the environmental level.

Device 85 can comprise, or be associated with data processing unit 94which processes or analyzes the data corresponding to the measuredquantities, as described above. The principles and operations of dataprocessing unit 94 of system 100 are similar, mutatis mutandis, to theprinciples and operations of data processing unit 94 of system 70. Forexample, device 85 can convert the measured quantities to digital dataand transfer the data to unit 94 for further processing, such as, butnot limited to, the analysis of data corresponding to opticalmeasurements.

Device 85 can be located at the desired monitoring location 83, or itcan communicate with monitoring location 83, for example, usingmeasuring conduit 80.

It is to be understood that although FIG. 9 a illustrates monitoringlocation 83 above cuff 76, this need not necessarily be the case, since,as stated, many other monitoring locations are contemplated. When theadditive is delivered to a location above the cuff, device 85 can samplegas directly from lumen 65 to determine presence of the additivetherein.

In the exemplified illustration of FIG. 9 a, the additive is deliveredthrough lumen 65 and device 85 communicates with location 83 via conduit80, and in the exemplified illustration of FIG. 9 b, the additive isdelivered through conduit 71 and device 85 communicates with lumen 65,either directly or indirectly, e.g., through the breathing machine orthe ventilator. It is to be understood that although FIG. 9 billustrates monitoring location 83 in or near the lungs, this need notnecessarily be the case, since many other monitoring locations arecontemplated as further detailed hereinabove.

Device 85 can also comprise one or more sensors 84 located at themonitoring location and configured to communicate with device 85 via acommunication channel, such as, but not limited to, measuring conduit80, which can be or include a suitable transmission line. The type ofsensors depends on the type of the measuring device.

System 100 can also comprise other components, such as, but not limitedto, suctioning device 86, suctioning conduit 88, inflating device 90 andalerting unit 92, as further detailed hereinabove.

Additional objects, advantages and novel features of the presentinvention will become apparent to one ordinarily skilled in the art uponexamination of the following example, which are not intended to belimiting. Additionally, each of the various embodiments and aspects ofthe present invention as delineated hereinabove and as claimed in theclaims section below finds experimental support in the followingexample.

EXAMPLE

Reference is now made to the following examples, which together with theabove descriptions illustrate the invention in a non limiting fashion.

In the present example, continuous assessment of leakage near theendotracheal tube cuff by monitoring CO₂ pressure (PCO₂) in the upperairway, in accordance with the teachings of the present embodiments.

The purpose of this study was to establish an accurate, objective,non-invasive bedside method for assessment of a leakage near theendotracheal tube cuff. Initially, the feasibility of the method wasinvestigated in a human simulator. Subsequently, leaks at various cuffpressures were evaluated by iodine leakage test in a porcine modelssimulating human airway mucosa. Finally, the feasibility of the methodwas evaluated in 60 patients undergoing elective surgery, comparing thenew method to the standard clinical evaluation used today.

Methods

Three anatomical locations were evaluated, in accordance with variousexemplary embodiments of the present invention: (i) between theendotracheal tube cuff and the vocal cords through a suction mini-guidelumen catheter attached externally to the endotracheal tube; (ii) at theoropharynx above the epiglottis by a catheter inserted through a plasticoropharyngeal airway; and (iii) in the nostrils through a nasal cannula.

FIG. 10 shows the anatomic locations of CO₂ sampling in the humansimulator and in patients under general anesthesia.

The study was performed in 3 phases. In phase 1 the feasibility of themethod in a human simulator was ascertained. In phase 2, the method in aporcine model was experimentally explored. In phase 3 the method wascompared with the standard technique for estimating optimal endotrachealtube cuff filling in 60 surgical patients under general anesthesia.

Throughout the three phases of the study, PCO₂ levels were recordedusing a micro-side-stream capnograph (Microcap®, Oridion, Jerusalem,Israel) with flow rate of 50 ml/min−7.5+15 ml/min and rise time to CO2step of about 0.2 s. The Microcap® utilizes an algorithm which detectsand saves only the end tidal PCO₂ values. In order to avoid inaccurateprocessing of PCO₂ data by the capnograph, the routinely utilizedalgorithm to detect end tidal PCO₂ was neutralized and all PCO₂ valueswere directly transported and saved on a data processor. Any increase ofmore than 1 mm Hg in PCO₂ reading was interpreted as a sign of leakagearound the cuff and the appropriate cuff pressure was set accordingly.This cuff pressure was automatically kept constant by a specialelectronic cuff pressure controller device (TRACOE® cuff pressurecontroller, Germany) with controlled accuracy of ±2 mbar, avoidingpossible cuff pressure changes due to fluctuations in inspiratorypressures or any other local variables. Endotracheal tubes with highvolume, low pressure cuffs having an external side attached mini-guidelumen which opens 1 cm above the cuff (Hi-Lo® Evac, Mallinckrodt, USA)were used. The proximal end of the suction mini-guide was connected tothe capnograph (see FIG. 10).

FIG. 11 shows the exhaled CO₂ pressure waveform in accordance withendotracheal tube cuff pressures as displayed during the first phase.The suction time (from the upper airways) is represented by the straightline of the CO₂ pressure waveform.

Phase 1—Human Simulator Model

A human simulator of a 70 kg man (Medical Education Technologies, Inc(METI) Sarasota, Fla.) was used. A Hi-Lo® Evac endotracheal tube No. 8was inserted into the human simulator trachea. The tracheal diameter atthe location of the endotracheal tube cuff was 25 mm. Exhaled airend-tidal CO₂ of 40 mm Hg was simulated by adjusting a continuous CO₂stream into the simulator lungs.

While ventilating the human simulator the cuff was sequentiallyinflated, 2 mm Hg at a time, and PCO₂ leakage level was measured at thethree anatomic sites (see FIG. 10). After each cuff pressure change theoropharynx was suctioned to prevent CO₂ remnants from alteringsubsequent measurements.

Phase 2—Porcine Model

Experiments were conducted according to the National Institute of HealthGuidelines for the Care and Use of Laboratory Animals. Two pigs, weight10 kg and 13 kg, underwent general anesthesia with a No. 7 endotrachealtube. CO₂ leakage was assessed by a 4 mm diameter catheter inserteddirectly through a small incision into the trachea 1 cm above theendotracheal tube cuff and below the vocal cords. The endotracheal tubecuff pressure was increased sequentially, 2 mm Hg at a time, and PCO₂was measured through the catheter. After each measurement the upperairway was suctioned so as to avoid any CO₂ remnants.

After reaching a steady cuff pressure with no PCO₂ readings at the upperairway, a tracheal “window” was surgically opened below the endotrachealtube cuff. Iodine solution (5 cc) was injected above the cuff and restedthere for 60 minutes while iodine leakage below the cuff was evaluatedthrough the tracheal “window” at different cuff pressure levels.Throughout the experiment (including the period of iodine leakagemeasurements) animals were maintained on the same positive pressureventilation and the endotracheal tube location and animal head and neckposition were not changed.

Phase 3—Human Subjects

Sixty consecutive adult patients undergoing elective surgery withbalanced generalized anesthesia (NO₂:O₂) were included in the study.Patients with history of cigarette smoking or dyspnea were preassessedby pulmonary function tests, so as to obtain a homogenous group ofpatients regarding to mechanical ventilation volumes and pressures. Ninepatients were excluded due to forced expiratory volume per second (FEV₁)or vital capacity less than 50% of predicted. The study protocol wasapproved by the local ethics committee and patients signed an informedconsent.

In all patients the intubation was performed by an anesthesiologist andthe endotracheal tube position inside the trachea was determinedaccording to the height of the patient using the following formula: thelength from the distal tip of the endotracheal tube to the right mouthangle (measured in cm)=[body height (in cm)/5]−13 [Cherng C H, Wong C S,Hsu C H, Ho ST. Airway length in adults: estimation of the optimalendotracheal tube length for orotracheal intubation. J Clin Anesth.2002; 14: 271-274].

After intubation, the anesthesiologist was requested to set the minimalendotracheal tube cuff pressure required to prevent leakage according toexhalation-inhalation volume difference and air leakage heard with thestethoscope around the cuff. The cuff pressure was considered optimal bythe anesthesiologist when there was no exhalation-inhalation volumedifference and no air leakage heard with the stethoscope using theminimal cuff pressure for 5 minutes. Once cuff pressure level wasconsidered optimal by the anesthesiologist, the PCO₂ was measuring atthe aforementioned 3 locations.

Based on the findings in the porcine model, optimal cuff filling wasdefined as the minimal cuff pressure required for avoiding a PCO₂leakage of more than 2 mm Hg proximal to the endotracheal tube cuff viathe external mini-guide lumen of the Hi-Lo® Evac endotracheal tube.Suction was performed through the plastic airway as needed and 2 minutesbefore each PCO₂ measurement. Continuous monitoring of PCO₂ from the 3anatomic locations was performed throughout the operation.

Statistics

Statistical SPSS™ software (version 10.0, SPSS Inc., Chicago, Ill.) wasused for all analyses performed. Categorical data are expressed innumbers and percentages forms. Continuous data are expressed asmeans±standard deviations and compared by a paired t-test. Regressioncoefficient (R) was calculated as a measurement of correlation betweenendotracheal tube cuff pressure and PCO₂ in the upper airways andexpressed as R². P values below 0.05 were considered significant.

Results Phase 1—Human Simulator Model

FIG. 11 illustrates an example of the exhaled PCO₂ waveform inaccordance with endotracheal tube cuff pressure as displayed on a PCmonitor in the human simulator model. A linear correlation was observedbetween the endotracheal tube cuff pressure and the PCO₂ measured abovethe cuff in all three anatomic locations: (i) between the cuff and thevocal cords, R²=0.954, p<0.0001; (ii) at the oropharynx above theepiglottis, R²=0.923, p<0.0001; (iii) at the nostrils, R²=0.911,p<0.0001.

FIG. 12 shows the correlation between endotracheal tube cuff pressuresand CO₂ levels measured between the cuff and the vocal cords. At anendotracheal tube cuff pressure of 26 mm Hg or higher, no PCO₂ wasrecorded at all 3 anatomic locations. At an endotracheal tube cuffpressure of 25 mm Hg, PCO₂ was detected only between the cuff and thevocal cords. Once the endotracheal tube cuff pressure reached 24 mm HgCO₂ leakage was measured at all locations. At all levels of cuffpressures the maximal difference in PCO₂ readings between the variousanatomic locations was less than 2 mm Hg.

Phase 2—Porcine Model

FIGS. 13 a-b show correlation between endotracheal tube cuff pressureand upper airway CO₂ levels in the two porcine models. The black arrowmarks the point at which iodine solution leakage was first detected.

In animal “A” (FIG. 13 a) the minimal cuff pressure needed to preventCO₂ leakage was 28 mm Hg while the minimal cuff pressure needed toprevent iodine solution leakage around the cuff was 24 mm Hg, a pressureat which a PCO₂ leakage of 2-3 mm Hg was already measured. There was alinear correlation between endotracheal cuff pressure and PCO₂ leakageabove the cuff (R²=0.984, p<0.0001).

In animal “B” (FIG. 13 b) the minimal cuff pressure needed to preventCO₂ leakage around the endotracheal cuff was 30 mm Hg while the minimalcuff pressure needed to prevent iodine solution leakage around the cuffwas 25 mm Hg, a pressure at which a PCO₂ leakage of 3-4 mm Hg wasmeasured. There was a linear correlation between the endotracheal tubecuff pressure and PCO₂ leakage above the cuff (R²=0.988, p<0.0001).

Phase 3—Human Subjects

Baseline characteristics of the patients are summarized in Table 1,below.

TABLE 1 N = 60 Age (years)  58.5 ± 16.2* Sex (male/female) 44/16 Weight(kg)  79.4 ± 14.9* Height (cm) 168.9 ± 10.1* Patients with mildobstructive lung disease  6 (10%)^(†) Patients with mild restrictivelung disease  1 (2%)^(†) Tube size: 7.5 (mm ID) 20 (33%)^(†) 8 (mm ID)16 (27%)^(†) 8.5 (mm ID) 24 (40%)^(†) Peak inspiratory pressure (mm Hg) 21.2 ± 0.6* End-tidal CO₂ (mm Hg)  35.3 ± 2.4* Type of operationAbdominal laparoscopic surgery  4 (7%)^(†) Open abdominal surgery 22(37%)^(†) Orthopedic 22 (37%)^(†) Urological  2 (3%)^(†) Other 10(17%)^(†) *Data are expressed as means ± standard deviations. ^(†)Dataare expressed as numbers of patients (percentage in parentheses).

The mean age of the patients was 58.5±16.2 years. The mean peakinspiratory pressure was 21.2±0.6 mm Hg. Although patients with severepulmonary diseases were excluded from the study (FEV₁ or VC less than50% of predicted), six patients (10%) had mild obstructive lung diseaseand one patient had mild restrictive lung disease.

The results from the human simulator and the porcine model, demonstrateda linear correlation between PCO₂ leakage measurements and endotrachealtube cuff pressures. A PCO₂ leakage measurement was consideredclinically significant if it was higher than 2 mm Hg proximal to theendotracheal tube cuff via the external mini-guide lumen of the Hi-Lo®Evac ETT. This was due to the fact that iodine solution leakage occurredonly when the PCO₂ leakage readings were higher than 2 mm Hg.

FIG. 14 shows comparison between the initial mean endotracheal tube cuffpressure, determined clinically by the anesthesiologist using theaudible leakage test and exhalation-inhalation volume difference, to themean optimal cuff pressure determined by CO2 leakage monitoring. Themean initial endotracheal tube cuff pressure of all of the studypopulation, determined clinically by the anesthesiologist, wassignificantly higher than the mean optimal cuff pressure determined byupper airway PCO₂ leakage monitoring proximal to the endotracheal tubecuff, 25.2±3.6 vs. 18.2±7.8 mm Hg respectively, p<0.001.

FIG. 15 shows percentage of patients with initial endotracheal tube cuffpressure significantly higher, lower, or accurate compared to theoptimal cuff pressure determined by PCO₂ leakage monitoring (n=60).

In 43 patients (72%) the clinically determined endotracheal tube cuffpressure was significantly higher than the optimal cuff pressuredetermined by CO₂ leak, with a mean change of 10.2 mm Hg in cuffpressure, 25.4±3.9 vs. 15.2±4.7 mm Hg, p<0.0001.

In 8 patients (13%) the initial endotracheal tube cuff pressures weresignificantly lower than the optimal cuff pressure. Nine patients (15%)had an initial endotracheal tube cuff pressure similar to the optimalcuff pressure.

In 3 patients CO₂ leakage continued despite were exceptionally high cuffpressure, up to 35 mm Hg. The pressures determined by theanesthesiologist in these patients were 30, 32 and 33 mm Hg. Afterdistal repositioning of the endotracheal tube the cuff pressures neededto prevent CO₂ leakage were reduced to less than 30 mm Hg similar to therest of the study population. Since cuff pressures required for completesealing were reduced dramatically after distal reposition, it wasassumed that the primary incomplete sealing, was probably due to a veryhigh proximal airway position causing mal contact between theendotracheal tube cuff and the patient airway anatomy (e.g., directcontact between the cuff and the vocal cords).

During surgery a new leakage of CO₂ around the endotracheal tube cuffdeveloped in 16 patients (27%) attributable to variable causes such asincreased peak inspiratory pressure by more than 5 mm Hg due tolaparoscopic surgery with abdominal gas inflation, light anesthesia orinadequate neuromuscular blockade, change of head position due tosurgical requirements and ETT movement during surgery.

Table 2, below summarizes the causes of a “new” leakage duringoperation.

TABLE 2 Increase in peak inspiratory pressure 10/11 Gas inflation of theabdomen 4/4 Inadequate neuromuscular block 3/4 Light anesthesia 3/3Change of patients' head position 5/9 Change of tube position 1/2

During surgery CO₂ recordings were obtained at all 3 anatomicallocations and differences in PCO₂ readings were less than 2 mm Hg. Aftera mean of 9±4 measurements through the suction mini-guide catheterattached to the endotracheal tube, no further readings could be obtaineddue to obstruction by secretions so further PCO₂ readings were obtainedonly from the plastic airway (hypopharynx) and from the nares.

DISCUSSION

Methods used today to determine adequate cuff filling are eitherinaccurate or cumbersome [Petring O U, Adelhoj B, Jensen B N, et al.Prevention of silent aspiration due to leaks around cuffs ofendotracheal tubes. Anesth Analg 1986; 65:777-780; Young P J, Basson C,Hamilton D, Ridley S A. Prevention of tracheal aspiration using thepressure-limited tracheal tube cuff. Anaesthesia 1999; 54: 559-563].

In this study the determining of the appropriate endotracheal tube cufffilling was performed by continuous CO₂ pressure (PCO₂) monitoring atthe upper airway, in accordance with the teachings of the presentinvention. The linear correlation found between the endotracheal tubecuff pressure and CO₂ leakage above the cuff shows that PCO₂ can be usedas a quantitative indicator of air leak. Although there was an overalllinear correlation between endotracheal tube cuff pressure and PCO₂ inthe upper airways (R²>0.91, p<0.0001 for all 3 anatomical locations),the correlation seems less linear at the beginning and at the end of thecurve with lower PCO₂ changes than expected compared to the increase incuff pressure. The observed non-linearity can be explained by the widedynamic range (0-40 mm Hg) and relatively low sensitivity (±1 mm Hg) ofthe capnograph. This non-linearity can be avoided or reduced using acapnograph having a lower dynamic range (e.g., 0-10 mm Hg) and a highersensitivity (e.g., 0-1 mm Hg).

The rational for this observation can be that at the very low cuffpressures there is still a considerable volume allowing continuous CO₂leak, and at the high cuff pressures, with minimal CO₂ leak, there is aneed for higher changes in cuff pressures in order to achieve completesealing of the trachea by the cuff.

In phase 2 of the present study a porcine model was used assessingiodine leakage around the cuff. As iodine is less viscous thanpharyngeal secretions it was assumed that the cuff pressure needed toprevent iodine leakage is sufficient to prevent secretion leakage aroundthe endotracheal tube cuff. In this model, using sequential increases of2 mm Hg in cuff pressure, iodine leakage occurred only when PCO₂readings were higher than 2 mm Hg, suggesting that PCO₂ leakage test hasa safety margin of 2 mm Hg. Based on these findings and considering thatmaximal change in PCO₂ measurements between the 3 locations was lessthan 2 mm Hg, it was concluded that for clinical practice measurementsof PCO₂ at the oropharynx or the nostrils are equivalent to distalmeasurements just above cuff. The second phase of the study wasconducted in only two pigs due to limitations and restrictions by theNational Institute of Health Guidelines for the Care and Use ofLaboratory Animals. Differences between the cuff pressure needed toprevent CO₂ leakage and that needed to prevent iodine leakage in bothpigs were almost identical and it seemed inappropriate to sacrifice moreanimals for this model.

In the third phase of the study the method was evaluated in patientsundergoing elective surgery under general anesthesia. The mean initialendotracheal tube cuff pressure determined clinically by theanesthesiologist was significantly higher than the optimal cuff pressureassessed by CO₂ leakage monitoring. In all patients, 25.2±3.6 vs.18.2±7.8 mm Hg, p<0.001; in 72% of the patients, primary endotrachealtube cuff pressures were significantly higher than the optimal cuffpressure determined by PCO₂ readings, with a mean change of 10.2 mm Hg.

Although the general tendency of the anesthesiologists was to“overshoot” the initial cuff pressure, in 13% of the cases lower thanoptimal initial cuff pressures was found. Moreover, during surgery, a“new” leakage developed in 27% of the patients, potentially exposingthem to aspiration risk. This variability in cuff pressure, observedeven in stable elective surgery patients, emphasizes the need for anaccurate, continuous bedside method to determine the appropriate cuffpressure.

An important problem encountered during the study was obstruction bysecretions of the mini-guide lumen of the Hi-Lo® Evac ETT after severalaspirations for PCO₂ measurements despite suctioning of the upperairways. In contrast, PCO₂ readings through nasal cannula or from theoropharynx through the plastic airway were easily obtained aftersecretion clearance by oral suctioning.

Another important issue regards the position of the endotracheal tube.Malpositioned endotracheal tube is hazardous for intubated patients.Insertion of an endotracheal tube too distally leads to endobronchialintubation, which may cause collapse of the contralateral lung, whileproximal insertion may lead to accidental extubation or vocal cordtrauma [Streitz J M Jr, Shapshay S M. Airway injury after tracheotomyand endotracheal intubation. Surg Clin North Am 1991; 71:1211-1230].Several formulae and other methods have been proposed to estimate theoptimal length for endotracheal tube insertion [Owen R L, Cheney F W.Endobronchial intubation: a preventable complication. Anesthesiology1987; 67:255-257; Mehta S. Intubation guide marks for correct tubeplacement. A clinical study. Anaesthesia 199; 46:306-308; Patel N,Mahajan R P, Ellis F R. Estimation of the correct length of trachealtubes in adults Anaesthesia. 1993; 48:74-75; Cherng C H, Wong C S, Hsu CH, Ho S T. Airway length in adults: estimation of the optimalendotracheal tube length for orotracheal intubation. J Clin Anesth.2002; 14:271-274]. However, none is always satisfactory.

In the current study, 3 patients had a CO₂ leakage despite exceptionallyhigh (>35 mm Hg) cuff pressures. However, pressure decreased to lessthan 30 mm Hg (as has been in the rest of the study population) afterdistal repositioning of the endotracheal tube. Although it was not theaim of the study, continuously CO₂ leakage near an appropriatelyinflated cuff can be used as a marker for malpositioned endotrachealtube. Incessant CO₂ leakage around the endotracheal tube cuff can occurwhen there is incomplete sealing due to mal contact with the vocalcords, endobronchial intubation (CO₂ from the contralateral lung) orabove vocal cord intubation.

It is appreciated that certain features of the invention, which are, forclarity, described in the context of separate embodiments, may also beprovided in combination in a single embodiment. Conversely, variousfeatures of the invention, which are, for brevity, described in thecontext of a single embodiment, may also be provided separately or inany suitable subcombination.

Although the invention has been described in conjunction with specificembodiments thereof, it is evident that many alternatives, modificationsand variations will be apparent to those skilled in the art.Accordingly, it is intended to embrace all such alternatives,modifications and variations that fall within the spirit and broad scopeof the appended claims. All publications, patents and patentapplications mentioned in this specification are herein incorporated intheir entirety by reference into the specification, to the same extentas if each individual publication, patent or patent application wasspecifically and individually indicated to be incorporated herein byreference. In addition, citation or identification of any reference inthis application shall not be construed as an admission that suchreference is available as prior art to the present invention.

What is claimed is:
 1. An alerting and controlling system, the systemcomprising: a measuring device connectable to an endotracheal tubeassociated with a cuff inflatable below the vocal cords of a subject,for measuring at least one measure being indicative of the presence ofleakage of secretions from above said cuff to the lungs of the subject;and a controller configured for adjusting inflation of said cuffresponsively to said level of said at least one measure such as toreduce or prevent leakage of secretions from above said cuff to thelungs, and for alerting that said endotracheal tube is malpositioned inthe airway of the subject if an inflation pressure of said cuff exceedsa predetermined threshold.
 2. The system of claim 1, further comprisingsaid endotracheal tube and said cuff.
 3. The system of claim 1, whereinsaid at least one measure comprises carbon dioxide concentration betweensaid cuff and said vocal cords.
 4. The system of claim 1, wherein saidat least one measure comprises carbon dioxide concentration above saidvocal cords.
 5. The system of claim 1, wherein said at least one measurecomprises carbon dioxide concentration at a nostril of the subject. 6.The system of claim 1, wherein said at least one measure comprisesacoustical data being indicative of leakage near said cuff outside saidendotracheal tube.
 7. The system of claim 1, wherein said at least onemeasure comprises pressure data being indicative of fluid flow in aleaking duct near said cuff outside said endotracheal tube.
 8. Thesystem of claim 1, wherein said at least one measure comprises flow databeing indicative of fluid flow in a leaking duct near said cuff outsidesaid endotracheal tube.
 9. The system of claim 1, wherein said at leastone measure comprises optical data being indicative of presence ofsecretions near said cuff outside said endotracheal tube.
 10. The systemof claim 1, wherein said at least one measure comprises electricalcharacteristics of fluid above said cuff outside said endotracheal tube.11. The system of claim 1, further comprising an additive deliveringdevice configured for delivering at least one identifiable additivethrough said endotracheal tube, wherein said at least one measurecomprises presence or concentration of said at least one identifiableadditive.
 12. The system of claim 11, wherein said at least oneidentifiable additive is characterized by measurable electricproperties.
 13. The system of claim 11, wherein said at least oneidentifiable is characterized by measurable magnetic properties.
 14. Thesystem of claim 11, wherein said at least one identifiable ischaracterized by measurable optical properties.
 15. The system of claim11, wherein said at least one identifiable is characterized bymeasurable radiation properties.
 16. The system of claim 11, whereinsaid at least one identifiable is characterized by measurablefluorescent properties.
 17. The system of claim 11, wherein said atleast one identifiable additive comprises at least one inert gas. 18.The system of claim 11, wherein said at least one identifiable additivecomprises at least one colored gas.
 19. The system of claim 11, whereinsaid at least one identifiable additive comprises at least oneradioisotope.
 20. The system of claim 1, wherein said controller isconfigured for alerting when said leakage is detected.